Defining the cellular and molecular processes underlying neuronal plasticity is critical to understanding the pathophysiology of drug abuse. To this end, we plan to focus on two lines of research involving key intracellular signaling processes implicated in fundamental aspects of neuronal plasticity: signaling via the Rho family of small G proteins and processing of dendritic RNA. Recent studies have provided compelling evidence that Rho proteins play a critical role in morphological changes underlying neuronal plasticity. My laboratory has identified a novel member of the RhoGEF family of proteins, the major regulators of Rho protein activity. In preliminary studies, we have found that this protein, referred to as Tech, is highly enriched in neurons of the hippocampus and cortex. Accordingly, we plan to: 1) characterize the RhoGEF activity of Tech, 2) assess the effect of Tech constructs on the morphology of hippocampal and cortical neurons, and 3) identify proteins that interact with Tech using the yeast two-hybrid system. Recent studies from my laboratory and others have identified Translin as an RNA binding protein implicated in dendritic RNA processing. In preliminary studies, we have identified the L7 dendritic transcript as a candidate target of Translin. Accordingly, we plan to: 1) conduct studies aimed at identifying other candidate Translin targets, and 2) generate mice deficient in Translin to assess its role in processing of L7 and other dendritic RNA transcripts.